Familial CD3+ T large granular lymphocyte leukemia: evidence that genetic predisposition and antigen selection promote clonal cytotoxic T-cell responses.

Abstract

CD3+ T-large granular lymphocyte (T-LGL) proliferations often present with cytopenias and splenomegaly and are linked to autoimmunity, especially rheumatoid arthritis and Felty's syndrome. We report here the intra-family occurrence of T-LGL leukemia in a father and son, both presenting with cytopenias and splenomegaly. Both patients carried the HLA-DRB1*04 allele, strongly associated with rheumatoid arthritis and Felty's syndrome, exhibited distinctive histopathological features suggestive of immune-mediated suppression of hematopoiesis and expressed a remarkably skewed T-cell receptor beta chain gene repertoire with overtime evolution (clonal drift). Immunoinformatics analysis and comparisons with clonotype sequences from various entities revealed (quasi)identities between (i) father and son, and (ii) father or son and patients with autoimmune disorders, T-LGL leukemia or chronic idiopathic neutropenia. Altogether, our results further corroborate antigen selection in the ontogeny of T-LGL leukemia and point to the interplay between genetics and the (micro)environment in shaping the outcome of cytotoxic T cell responses.

• Authors: Evangelia Stalika, Apostolia Papalexandri, Michalis Iskas, Niki Stavroyianni, George Kanellis, Konstantina Kotta, Charalambos Pontikoglou, Alexandra Siorenta, Achilles Anagnostopoulos, Helen Papadaki, Theodora Papadaki, Kostas Stamatopoulos
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 55 Issue 8 Pg. 1781-7 (Aug 2014) ISSN: 1029-2403 [Electronic] United States
• PMID: 24180333 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD3 Complex
• Receptors, Antigen, T-Cell, alpha-beta
• STAT3 Transcription Factor

Topics

• Adult
• Bone Marrow (metabolism, pathology)
• CD3 Complex (genetics, immunology, metabolism)
• Clonal Selection, Antigen-Mediated (genetics, immunology)
• Family
• Genetic Predisposition to Disease
• Histocompatibility Testing
• Humans
• Immunohistochemistry
• Immunophenotyping
• Leukemia, Large Granular Lymphocytic (diagnosis, genetics, immunology)
• Male
• Middle Aged
• Mutation
• Receptors, Antigen, T-Cell, alpha-beta (chemistry, genetics, metabolism)
• STAT3 Transcription Factor (genetics, metabolism)
• Spleen (metabolism, pathology)
• T-Lymphocyte Subsets (immunology, metabolism)
• T-Lymphocytes, Cytotoxic (immunology, metabolism)